Function of the Myo-adipo Axis in Human Obesity and Type 2 Diabetes
肌脂肪轴在人类肥胖和 2 型糖尿病中的功能
基本信息
- 批准号:8793748
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-04-01 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAdipocytesAdipose tissueAnti-Inflammatory AgentsAnti-inflammatoryApoptosisAttentionBehaviorBiopsyBlood capillariesBody CompositionCellsCharacteristicsCommunicationDiabetes MellitusDyslipidemiasEndocrineEvaluationExperimental DesignsFat BodyFatty AcidsFatty acid glycerol estersFunctional disorderGene ExpressionGeneticGlucose IntoleranceHealthcare SystemsHumanIL8 geneIn VitroIndividualInflammationInflammation MediatorsInflammatoryInsulinInsulin ResistanceInterleukin-15LeadLearningLevel of EvidenceLipidsLipolysisMessenger RNAMetabolicMetabolic syndromeMetabolismMolecularMuscleMuscle CellsMuscle FibersMuscle functionNeutrophil InfiltrationNon-Insulin-Dependent Diabetes MellitusObesityOperative Surgical ProceduresOutcomePalmitatesParticipantPioglitazonePopulationProcessProductionPropertyProteinsRecruitment ActivityRegulationSignal PathwaySignal TransductionSiteSkeletal MuscleSourceStem cellsSystemTestingTherapeutic InterventionTimeTissue DifferentiationTissuesVisceraladipocyte differentiationadipokinesangiogenesisautocrinebehavior influencecapillarycytokinediabeticextracellularglucose metabolismglucose tolerancehuman tissueimprovedin vivoinsulin sensitivityinsulin signalinginterestlipid biosynthesislipid metabolismmacrophagemonocytenon-diabeticparacrinepatient populationprotein expressionrelease factorsatellite cellsubcutaneoustherapy designtissue culturevastus lateralis
项目摘要
DESCRIPTION (provided by applicant):
Metabolic dysfunction in obesity and type 2 diabetes (T2D) involves insulin resistance in multiple tissues. Recently key roles in metabolic regulation have been identified for factors produced by and secreted from adipose tissue (termed adipokines) that can either induce insulin resistance or improve insulin sensitivity. Less attention has been paid to factors produced by skeletal muscle (myokines) that could also influence insulin sensitivity, as well as impact adipose tissue (AT) accumulation and function. The hypothesis to be tested is: Skeletal muscle produces and releases factors (myokines) that can act in an autocine manner on muscle to augment or impede metabolism and insulin action as well as act in an endocrine manner to influence AT metabolism and accumulation. Muscle from obese type 2 diabetic individuals produces more of the myokines that induce insulin resistance and stimulate fat accumulation. There are 3 Specific Aims.1) Determine the ability of human skeletal muscle to produce and secrete GRO¿, IL-8, and IL-15 and regulation of this production by inflammatory and anti- inflammatory signals. 2) Establish the autocrine effects of these specific myokines on glucose metabolism and insulin sensitivity in skeletal muscle, and the signaling pathways involved. Are diabetic muscle cells more or less sensitive to the actions of these myokines? 3) Evaluate the effects of specific myokines on the differentiation and apoptosis of adipocytes, angiogenesis in AT, and lipid metabolism, with an emphasis on potential depot (subcutaneous vs visceral) differences and the impacts of obesity and T2D. This project will be performed totally in humans, their tissues and cells derived from those tissues. Insulin action in skeletal muscle will be studied both in vivo and in vitro in muscle tissue and cultured muscle cells and adipose tissue. Muscle and AT biopsies will be obtained for evaluation of the content of GRO¿, IL-8, and IL-15 mRNA and protein. Satellite cells from the biopsies will be propagated in culture and differentiated into myotubes to evaluate muscle specific production of the myokines of interest. Myotubes will also be treated with inflammatory and anti-inflammatory signals as well as individual myokines to determine if responsiveness to the factors varies with diabetes. Expression of the factors in myotubes will also be manipulated by genetic means. AT will be maintained in culture, treated with the proposed myokines of interest and both adipogenesis and apoptosis of mature adipocytes followed. AT will also be treated with individual myokines to follow effects on angiogenesis. Results from this project will provide molecular mechanisms for metabolic dysfunction seen in vivo in obesity and T2D and identify possible targets for therapeutic interventions.
描述(由申请人提供):
肥胖和 2 型糖尿病 (T2D) 的代谢功能障碍涉及多个组织中的胰岛素抵抗,最近已确定脂肪组织产生和分泌的因子(称为脂肪因子)在代谢调节中的关键作用,这些因子可以诱导胰岛素抵抗或提高胰岛素敏感性。人们对骨骼肌(肌因子)产生的因素关注较少,这些因素也可能影响胰岛素敏感性以及脂肪组织(AT)的积累和功能。要检验的假设是:骨骼肌产生和释放。可以以自分泌方式作用于肌肉以增强或阻碍代谢和胰岛素作用以及以内分泌方式影响 AT 代谢和积累的因子(肌因子)来自肥胖 2 型糖尿病个体的肌肉产生更多的肌因子,从而诱导。胰岛素抵抗和刺激脂肪积累有3个具体目标。1)确定人体骨骼肌产生和分泌GRO的能力。 、IL-8 和 IL-15 以及炎症和抗炎信号对这种产生的调节 2) 确定这些特定肌因子对骨骼肌葡萄糖代谢和胰岛素敏感性的自分泌作用以及所涉及的信号传导途径。对这些肌因子的作用或多或少敏感? 3) 评估特定肌因子对脂肪细胞分化和凋亡、AT 血管生成和脂质代谢的影响,重点是潜在储存库(皮下与内脏)差异以及肥胖和 T2D 的影响 该项目将完全在人体中进行,将在体内和体外研究骨骼肌中的胰岛素作用。将获得肌肉组织和培养的肌肉细胞以及脂肪组织以评估 GRO¿ 、IL-8 和 IL-15 mRNA 和蛋白质将在培养物中增殖并分化为肌管,以评估感兴趣的肌因子的肌肉特异性产生。肌管也将接受炎症和抗炎信号处理。以及个体肌因子,以确定对这些因素的反应是否随糖尿病而变化。肌管中这些因素的表达也将通过遗传手段维持在培养物中,并用所提出的方法进行治疗。感兴趣的肌因子以及随后的成熟脂肪细胞的脂肪生成和凋亡也将用单独的肌因子进行处理,以跟踪对血管生成的影响,该项目的结果将提供肥胖和 T2D 体内代谢功能障碍的分子机制,并确定可能的靶点。治疗干预。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Robert Roy Henry其他文献
Robert Roy Henry的其他文献
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{{ truncateString('Robert Roy Henry', 18)}}的其他基金
Epicatechin and derivatives to preserve muscle structure function in diabetes
表儿茶素及其衍生物可保护糖尿病患者的肌肉结构功能
- 批准号:
8630186 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Epicatechin and derivatives to preserve muscle structure function in diabetes
表儿茶素及其衍生物可保护糖尿病患者的肌肉结构功能
- 批准号:
9199413 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Epicatechin and derivatives to preserve muscle structure function in diabetes
表儿茶素及其衍生物可保护糖尿病患者的肌肉结构功能
- 批准号:
8820260 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin
表儿茶素的早期临床前和初步临床研究
- 批准号:
8719394 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Function of the Myo-adipo Axis in Human Obesity and Type 2 Diabetes
肌脂肪轴在人类肥胖和 2 型糖尿病中的功能
- 批准号:
8460420 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Function of the Myo-adipo Axis in Human Obesity and Type 2 Diabetes
肌脂肪轴在人类肥胖和 2 型糖尿病中的功能
- 批准号:
8698393 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Function of the Myo-adipo Axis in Human Obesity and Type 2 Diabetes
肌脂肪轴在人类肥胖和 2 型糖尿病中的功能
- 批准号:
8329140 - 财政年份:2012
- 资助金额:
-- - 项目类别:
TARGETING INFLAMMATION USING SALSALATE FOR TYPE 2 DM
使用水杨酸针对炎症治疗 2 型糖尿病
- 批准号:
8166869 - 财政年份:2009
- 资助金额:
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GLUCOSE METABOLISM AND INSULIN ACTION IN HUMAN SKELETAL MUSCLE CULTURE
人体骨骼肌培养中的葡萄糖代谢和胰岛素作用
- 批准号:
7724880 - 财政年份:2007
- 资助金额:
-- - 项目类别:
EFFECT OF 12 WKS OF COLESEVELAM ON INSULIN SENSITIVITY & ORAL GLUCOSE ABSORPTION
12 周考来维仑对胰岛素敏感性的影响
- 批准号:
7724920 - 财政年份:2007
- 资助金额:
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